| 溶瘤病毒(oncolytic virus,OVs)研究进展与应用开发 |
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Sayed-AhmedMZ,etc.HealthSciJVol.12.No.4:579.全球溶瘤病毒研究概况T-vecbyA
MGEN全球溶瘤病毒研究概况IbrahimRagabEissaetc.Cancers2018,10,356溶溜腺病毒
（OntolyticAdenovirus，OA）开发腺病毒&腺病毒载体野生型腺病毒复制缺陷型腺病毒溶瘤腺病毒策略类型病毒衣壳改
造优化（提高感染效率，降低免疫原性，降低毒性）+基因治疗Gene-therapeuticOAE1B55KD缺失Fiber-mo
dification(Adaptor,Capsidevolution,etc.）Therapeuticgene-expre
ssionOA（exp53,IL-2,etc.）E1A24bp缺失Antibody-expressionOA肿瘤特异性
启动子启动E1表达（ex:pTert-E1)ImmuneCheckpointInhibitor-expressingOA(
PD-1/PD-L1antibody-OA)E1region-deletedadenovirusRNAinterferen
ce-OAOncolytic-Adenovirus（OA）早期开发策略ONYXinfectCellswithinactiv
atedp53pathwayONYXD24inE1D24inE1CellswithinactivatedpRB/
p16pathwayNoreplicationinfectp53infectinfectMutantE1MutantE1n
op53replicationreplicationnopRBblockpRBNoreplicationCellswith
intactp53pathwaylysislysisCellswithintactpRB/p16pathwayInf
ectadjacentcellsInfectadjacentcells溶瘤腺病毒策略类型Adenoviruswithd
eletedE1B55KDregion(ONYX)AdenoviruswithmutantE1A(D24)溶瘤腺病毒
策略类型Tumorspecific-promoterdependentoncolyticadenovirusAdapter
-basedadenovirusAdapterex:RGDmotif-bindtocellularintegrin
Oncolyticadenovirus病毒衣壳改造优化Fiber-modifiedadenovirusTherapeuti
cgeneinE3TherapeuticgeneproductEffectbystandereffectifrel
easeDE3D55kDE1BLysisandreleaseE1Oncolyticadenovirus+基因治疗Gene
therapeuticOncolyticAdenovirusGenetherapeuticOncolyticAdeno
virus(Ex:ONYXviruswithIL-2inE3)TherapeuticGenes:IL-2,HSV
tk,p53,TRAIL,etcTherapeuticAntibody:VEGFantibody,etcCheck-
pointinhibitor:AntibodyofPD-1,PD-L1,CTLA-4,etcRNA：shRNA，mic
roRNA,etc新OA发现新OA工艺开发新OA开发Fiber区改造、筛选、优化及验证PD/PK/Biodistributio
n小规模开发肿瘤特异性启动子筛选OA毒理中等到大规模工艺开发特异性启动子-E1区装载及有效性验证E1region-deleted
adenovirusOA-抗肿瘤靶点、免疫治疗靶点抗体装载及有效性初步验证药诺基因Oncolytic-Adenovirus（O
A）开发流程GLP级别的基因治疗技术开发平台人类基因组计划完成，基因序列和功能几乎全部已知；除了感染以外，人类的大部分疾病都来自父
母遗传（某个或某些基因出了问题）人类基因组计划完成，基因序列和功能几乎全部已知；除了感染以外，人类的大部分疾病都来自父母遗传（某个或某些基因出了问题） |
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